Lecture 24: Cellular immunity and histocompatibility Flashcards
Where is the immature thymocyte produced?
In the bone marrow
Where does the thymocyte develop?
In the thymus
What cells do the thymocytes form?
The immature thymocyte (shows CD4 and CD8) antigens forms the cytotoxic T lymphocyte (CD8) and helper T lymphocyte (CD4)
What are the types of T helper lymphocytes?
Treg - regulate immune response
Th1 - drive cellular immunity
Th2- cause B cells to make antibodies
Th17- innate response - generates inflammatory response
Where is the thymus located?
On top of pericardium above the heart
What is the role of the thymus in maturation of T lymphocytes?
The progenitor lymphoid cells are educated to recognise self MHC molecules
In this process many die from neglect
How does the body detect cells that have been infected with a virus?
Viral peptide is displayed as part of the major histocompatibility complex (MHC)
What is MHC?
Major histocompatibility complex is a set of highly polymorphic genes that code for human leukocyte antigens on the cell surface
How do killer T lymphocytes kill infected cells?
Cytotoxic T cells react to cells in the body when there is a change in MHC class I molecules - these will express a neo-antigen (viral or altered self antigen)
How was the existence of the MHC gene proven?
Formation of congenic strains of mouse by breeding a child (AB) to its parent (A or B) multiple times - only those offspring who rejected tissue transplants were continually bred.
This meant that the congenic mouse basically had the same genetics as their parent except for the one gene - MHC
T lymphocytes were extracted from these mice and its reaction with infected cells were observed
The T lymphocytes only recognised cells from its own strain proving the existence of this MHC
What is MHC restriction?
The idea that viral immunity requires presence and recognition of two antigens
Self - antigen encoded by MHC
Non-self - antigen encoded by virus
What is HLA?
Human leukocyte antigen - the surface antigen on body cells coded for by the MHC. These present peptide antigens to T cells
There are 6 different molecules that are expressed
Class I - A B C
Class II - DR DP DQ
What is CD4 and CD8?
Accessory molecules on T cells that physically associate with the T cell receptor
Where is CD4 found?
These are found associated with T cell receptors of helper T cells and recognize antigens in MHC class II
Where is CD8 found?
These molecules are found associated with T cell receptors of cytotoxic T cells and recognise antigens in MHC class I
What is the function of CD4 and CD8?
They have cytoplasmic tails associated with intracellular tyrosine kinases which allow them to initiate T cell signaling through activation of the phosphorylation cascade. Hence, they play an important role in activation of adaptive immune response
What do helper T cells do?
T cells proliferate and produce cytokines that help other cells
What do cytotoxic T cells do?
Produces granzyme and perforins that punch holes in the target cell membrane and destroy cell viability
What is the difference between MHC class I and II?
MHC Class I codes for the viral peptide which leads to a response from CD8 causing a cytotoxic response
MHC Class II codes for the bacterial peptide which leads to a response from CD4 causing a helper response
What is MHC polymorphism?
The variation of amino acids in the protein domains that form the peptide groove
An individual will express 2 x 3 MHC Class I and 2 x 3 MHC Class molecules - co-dominance (both paternal and maternal genes are expressed)
What are 2 consequences of polymorphism?
- Tissue transplantation is difficult except between identical twins
- MHC polymorphisms are strongly linked to many autoimmune diseases